Method for the relief of pain

ABSTRACT

There is disclosed an improved method for the relief in humans of pain which is susceptible to topical treatment comprising the topical application to the distressed areas of a person of an amount of an anesthetic composition effective to relieve said pain wherein the composition comprises captan and a surface-active bactericide. In its preferred embodiment, the bactericide comprises benzethonium chloride. The composition is preferably incorporated into a topical vehicle to facilitate its application to the distressed areas.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation-in-part of application Ser. No.029,698, filed Apr. 13, 1979, now U.S. Pat. No. 4,267,007, which was acontinuation of application Ser. No. 781,170, filed Mar. 25, 1977, nowabandoned.

BACKGROUND OF THE INVENTION

The present invention relates to a method of relieving pain and, inparticular, relates to an improved method for relieving the painresulting from minor burns, sunburn, insect bites, hives, scratches,scrapes, minor cuts and abrasions, and the pain associated with viralskin diseases susceptible of topical treatment such as herpes zoster.

Prior methods of treatment of viral skin diseases, such as herpeszoster, commonly known as shingles, have included the use of cortisone,steroids, anesthetics, ect. However, these methods of treatment havebeen generally unsuccessful. Applicant has previously described animproved method for the treatment of such viral skin diseases,comprising the topical application of a chemical composition to theinfected areas wherein the composition comprises captan and asurface-active bactericide. However, it has surprisingly been determinedthat the topical applications disclosed herein unexpectedly demonstrategeneral anesthetic properties which are useful in relieving pain whichis susceptible of topical application, such as minor burns, sunburn,scratches, scrapes, hives, and minor cuts and abrasions, in addition torelieving the pain associated with these viral skin diseases.

It is well known that herpes zoster is a viral disease which frequentlycauses excruciating, prolonged pain and discomfort. A typical shinglespatient suffers a great amount of pain for a period of six weeks to sixmonths. Further, other symptoms of the disease may continue for a yearor longer and in some cases even for the rest of the patient's life.Blindness, neuritis, and partial paralysis are some of the severedisabilities which can result from the disease. One particularly badcharacteristic of the ailment is that it tends to recur periodically,particularly in older patients.

To describe the disease in technical terms, the virus attacks one ormore sensory ganglia, usually on one side of the body but sometimes onboth. The inflammatory process can extend inward to the meninges andinto the root entry zone of the spinal cord; occasionally, it involvesthe ventral horns, resulting in lower motor neuron paralysis of more orless segmental distribution. The related peripheral nerve or nerves areinvolved by a true inflammatory neuritis. Encephalitis and myelitisoccasionally occur in debilitated patients.

The earlier symptom of herpes zoster is pain in the distribution of theaffected root or roots around the trunk, or as a linear strip on theupper or lower limb, or in one or more divisions of the trigeminalnerve. It involves the pinna, external auditory meatus, and anteriorpillar of the fauces in geniculate herpes. In rare instances, thedisease is painless. However, in most cases, the skin of the infectedzone is hypersensitive even before the rash appears. In some cases,muscular paralysis may appear within one or two weeks after the rash hasappeared. Such paralysis is uncommon except in the case of geniculateherpes, which is usually accompanied by facial paralysis resemblingBell's palsy.

Postherpetic neuralgia is a common sequel, particularly in patients overfifty. The pain is persistent, and is usually aggravated by emotion andfatigue. Initially, the skin is sensitive to touch, but after a year ortwo, this sensitivity disappears.

In ophthalmic herpes, there is special danger to the eye, which may insome cases have a secondary bacterial infection. This secondaryinfection can lead to panophthalmitis. Further, corneal opacities orglaucoma can also result from the herpes.

In most cases, herpes zoster occurs in otherwise healthy individuals.However, in a minority of cases, it occurs in a background of lymphoma,leukemia, carcinoma, radiation therapy, or the use of immunosuppressivedrugs.

The method disclosed herein provides long-term lasting relief of pain inhumans which is susceptible to topical treatment without beingaddictive, hallucinogenic or causing similar harmful side effects.

SUMMARY OF THE INVENTION

It is, therefore, an object of the present invention to provide animproved method for the relief of pain in humans which is susceptible totopical treatment.

It is another object of this invention to provide an improved method forthe relief in humans of the pain resulting from minor burns, sunburn,scratches, scrapes, hives, insect bites and minor cuts and abrasions.

These and other objects and advantages are obtained by topicallyapplying a chemical composition to the distressed areas wherein thecomposition comprises captan and a surface active bactericide. In itspreferred embodiment, the bactericide comprises benzethonium chloride.The composition is preferably incorporated into a topical vehicle tofacilitate its application to the distressed areas. The application ofthe composition to the distressed areas in many cases results in partialor complete relief of the pain.

A more thorough disclosure of the objects and advantages of the presentinvention is presented in the detailed description which follows.

DETAILED DESCRIPTION OF THE INVENTION

The present invention contemplates an improved method for the relief ofpain in humans which is the result of hives, insect bites, minor burns,sunburn, scratches, scrapes, minor cuts and abrasions, and the painassociated with viral skin diseases susceptible of topical treatment,such as shingles, herpes simplex I and II, and herpes zoster, comprisingthe application of a chemical composition to the distressed areaswherein the composition comprises captan and a surface activebactericide. In its preferred embodiment, the composition comprisescaptan and benzethonium chloride. The composition is preferablyincorporated into a topical vehicle to facilitate its application to thedistressed areas.

Captan is a known fungicide and bactericide and has the formulaN-(trichloromethylthio)-4-cyclohexene-1,2-dicarboximide. Suitablesurface active bactericides for the practice of the present inventionare quarternary ammonium salts represented by the general formula:##STR1## where: R is a dodecyl, hexadecyl, or other long-chain group; a,b, and c are small alkyl or aralkyl groups, or may represent linkage toN in the form of a pyridine ring; and X is a chloride, bromide, sulphateor methosulphate ion.

In particular, the quaternary ammonium salts are exemplified by alkyltrimethyl ammonium salts, alkyl benzyl methyl ammonium salts, and alkylpyridinium salts. The longchain radical represented by R is oftenderived from the readily available fatty acids, e.g., lauryl, myristyl,cetyl, stearyl, or fatty acid mixtures obtained from coconut oil,tallow, etc. The dodecylbenzyl group, the octylphenyl group and the likehave also been used for this purpose. Preferred quarternary ammoniumsalts include phemerol chloride, diaparene chloride, cetyl pyridiniumchloride, benzalkonium chloride, benzethonium chloride,methylbenzethonium chloride, thonzonium bromide, triclobisoniumchloride, and domiphen bromide. However, it will be obvious to oneskilled in the art that other types of surface active bactericides mayalso be utilized in combination with captan in the practice of thepresent invention.

The composition is preferably incorporated into a topical vehicle tofacilitate its application to the infected areas. The topical vehiclefunctions to dilute the active ingredient and also functions to assistin the absorption of the active ingredients into the skin. Preferably,the vehicle is capable of dissolving substantial amounts of both thecaptan and the surface active bactericide to form a topical preparation.Suitable vehicles are absorbent, emulsion and oleaginous ointment basessuch as hydrophilic petrolatum, anhydrous lanolin, lanolin, hydrophilicointment, cold cream, petrolatum, propylene glycol, polyoxyl stearate,glycol ethers and derivatives, cetyl and stearyl alcohol, stearic acid,mineral oils, caster oil, glycerin, polyethylene glycol, animal oil andvegetable oils such as olive oil, corn oil, peanut oil, and cocoabutter. Other suitable vehicles are Brij 30 and Brij 35 (Brij is atrademark which was registered by the Atlas Powder Company, Wilmington,Del. The product is described in The Merk Index, 9th Edition (1976) atpage 177, paragraph 1377, and is a series of polyoxyethylene ethers offatty alcohols which include derivatives of cetyl stearyl and oleylalcohols, each ethoxylated with 2, 10, or 20 moles of ethylene oxide,and a lauryl alcohol, ethoxylated with 4 or 23 moles of ethylene oxide).Combinations of one or more of the above vehicles may also be utilizedin the practice of the present invention. However, it will be obvious toone skilled in the art that other suitable topical vehicles may also beutilized in the practice of the present invention.

It will be obvious to one skilled in the art that the topical vehiclemay also comprise, in addition to bodying agents, humectants,saponifying agents, emulsifiers, solvents, penetrants, pH regulators,plasticizers, emollients, preservatives, hardening agents, pigments anperfumes.

In the practice of the present invention, it is preferred that thetopical preparation further comprise a stabilizer to preventdecomposition of the active ingredients. Suitable stabilizers for thepractice of the present invention are butylated hydroxytoluene (BHT) andtocopherol. However, it will be obvious to those skilled in the art thatother suitable stabilizers may also be utilized in the practice of thepresent invention.

The topical preparation preferably contains an effective amount ofcaptan, e.g., from about 10 percent by weight to about 0.01 percent byweight, preferably about 1 percent by weight, and an effective amount ofthe surface active bactericide, e.g., from about 3 percent to about 0.01percent by weight, preferably about 0.1 percent by weight. Thepreparation further preferably contains an effective amount ofstabilizer, e.g., from about 0.5 percent by weight to about 0.005percent by weight, preferably about 0.02 percent by weight. In thisregard, it should be noted that increasing the concentration of thecaptan and the surface active bactericide in the preparation can causeirritation of the skin and in some cases allergic reactions. Thus, it ispreferred that a minimum amount of both compounds which enableseffective action and avoids allergic reaction be incorporated into thepreparation. However, it will be obvious to one skilled in the art thatfor more recalcitrant conditions, it may be desired to increase theamount of the active ingredients in the preparation to enable effectiveaction. Suitable topical preparations for the practice of the presentinvention are as follows:

    ______________________________________                                        I.        Captan          1.00%*                                                        Benzethonium Chloride                                                                         0.10                                                          BHT             0.02                                                          Brij 30         10.00                                                         Brij 35         10.00                                                         Cetyl Alcohol   10.00                                                         Petrolatum      68.88                                                                         100.00%                                             II.       Captan          3.00%                                                         Benzethonium Chloride                                                                         0.03                                                          BHT             0.02                                                          Castor Oil      10.00                                                         Brij 35         10.00                                                         Cetyl Alcohol   10.00                                                         Petrolatum      66.68                                                                         100.00%                                             III.      Captan          5.0%                                                          Benzethonium Chloride                                                                         0.4                                                           BHT             0.0                                                           Corn Oil        30.0                                                          Petrolatum      64.5                                                                          100.0%                                              IV.       Captan          1.00%                                                         Benzethonium Chloride                                                                         0.10                                                          BHT             0.00                                                          Brij 30         7.50                                                          Brij 35         7.50                                                          Cetyl Alcohol   7.50                                                          Caster Oil      7.50                                                          Petrolatum      68.88                                                                         100.00%                                             ______________________________________                                    

The topical composition is preferably spread thinly over the distressedareas of the skin and is preferably applied once or twice a day untilthe pain disappears. With respect to the treatment of the pain resultingfrom minor burns, sunburn, scratches, scrapes, hives, and minor cuts andabrasions, relief is often received shortly after the initialapplication, and the pain often disappears thereafter. In the treatmentof shingles, upon the application of the agent to the infected areas,the pain is often alleviated in a matter of seconds or minutes and thelesions and rashes begin to heal. With the palliation of pain, thepatient can usually sleep comfortably, wear conventional clothes, andlead a generally normal life. Eventually, the treatment results inremission.

In the treatment of shingles and herpes simplex I and II, the presentmethod is most effective when the topical agent is applied during theearly, active stages of the disease. Thus, in the treatment of shingles,the topical agent is preferably applied to the infected areas during thefirst six weeks following the onset of the symptoms of shingles. Whenthe agent is applied more than six weeks, and more particularly, morethan two months after onset of the symptoms of shingles, in some cases,the application of the agent does not result in palliation. It isbelieved that this is because the disease has by that time run itscourse and there only remains the aftereffects of the disease.

Although the rationale for the successful results of the present methodare not fully understood, it is believed that the captan and the surfaceactive bactericide cooperate synergistically to form a combination whichenables an effective anesthetic action against pain which is susceptibleof topical treatment. This effect is obtained even though neitheringredient itself is analgesic or anesthetic.

The composition of the present invention has been tested on severalpatients suffering from shingles or the pain resulting from minor burns,insect bites, or similar skin irritations. In each case of shingles, thediagnosis was made by a medical doctor. In all cases, a topical agentcorresponding to that of Example I was applied topically to thedistressed areas of the skin. However, in some cases, the preparationcontained no stabilizer (BHT) and in those cases the percentage ofpetrolatum was 68.90. The topical preparation was prepared by combiningthe three alcohols (Brij 30, Brij 35, and cetyl) and the petrolatum in avessel, and then gradually raising the temperature to about 125 degreesF. to melt the alcohols and the petrolatum. Purified captan,benzethonium chloride and BHT were then added to the melt with stirringand dissolved in the alcohols. The melt was then cooled with stirring toproduce a homogeneous mass of ointment having the general appearance andconsistency of petrolatum. The following are case histories of thetreatment of these patients. It is to be understood that these historiesare given by way of illustration and not of limitation.

CASE HISTORY NO. I

A white adult male suffered a burn while lighting his barbeque when thesulphur from the match stuck to his thumb. He immediately applied thetopical preparation of the present invention, and within a coupleminutes of application, the burning sensation completely disappearedfrom his thumb. A slight white mark remained on his thumb for two daysbut without the presence of pain.

CASE HISTORY NO. II

A white adult female received several deep scratches resulting fromcontact with blackberry vines. A liquid antiseptic was first sprayedover the distressed area which initially deadened the pain, but soonthereafter the pain bacame so severe that the subject could not tolerateany cloth next to the distressed area. About five minutes after applyingthe topical preparation of the present invention, the pain disappearedand did not return.

CASE HISTORY NO. III

A white adult female received a burn on her forearm from reaching intoan oven. Application of the topical preparation of the present inventionalleviated the pain resulting therefrom.

CASE HISTORY NO. IV

A family, including adults and grandchildren, suffered from sunburn andmosquito bites. Relief from the resulting pain was achieved by theapplication of the topical preparation of the present invention, whichalso relieved the corresponding itching from the mosquito and gnatbites.

CASE HISTORY NO. V

A white adult male suffered from a severe case of phlebitis which causedextreme itching. The application of the topical preparation of thepresent invention relieved the discomfort caused by the itching.

CASE HISTORY NO. VI

A white female developed herpes zoster of the cervical plexus of herneck. Five days after the onset of the ailment, the topical preparationof the present invention was applied to the infected areas. On the dayfollowing application of the ointment, the pain disappeared and thelesions began to dry out. Her only remaining symptom was a slightitching. All symptoms had disappeared within eleven days after onset ofthe disease.

CASE HISTORY NO. VII

A white female developed herpes zoster while hospitalized for treatmentof bleeding gastric ulcers. The infected area was on her right side,adjacent the 4-5 lumbar vertebrae. The symptom of the disease was asmall area of blisters which gradually extended toward the right, in aband about two inches wide and seven inches long. She experienced severeitching, burning and pain. Application of the topical preparation of thepresent invention gave immediate relief from pain and the eruptiondisappeared within about one week after application.

CASE HISTORY NO. VIII

A white adult female developed severe pain during a particular day, andby that night, the skin on her buttocks and the back of her thighs wasvery sore, and there were spots on her left side. She was unable to sitdown with comfort. The topical preparation of the present invention wasapplied to the infected area and it substantially alleviated the pain.Three days later she returned to the doctor who had originally diagnosedthe ailment as shingles and the doctor found her condition muchimproved.

CASE HISTORY NO. IX

A white adult female had suffered from shingles over a period of severalyears and in some years it had recurred several times during the year.No previous remedy had offered any relief. The topical preparation ofthe present invention was applied to the infected areas and the itchingand the burning pain promptly diminished to the point where the patientfelt comfortable. She maintained the area "moist" with a preparation,which seemed to shorten the distress period. The disease hassubsequently recurred periodically, but less frequently than prior tothe first application of the preparation of the present invention.

CASE HISTORY NO. X

A white adult female suffered from itching and knifing pains, and had arash four to five inches wide on each side of her breasts. The case wasdiagnosed by a doctor as a well-segmented case of shingles which wouldbe expected to last about six weeks to six months. The topicalpreparation of the present invention was applied two days after onset ofthe itching and pains and the first application relieved both itchingand pains. With additional applications, the rash completely disappearedin approximately two weeks after onset of the ailment.

CASE HISTORY NO. XI

An adult male had red blotches on the neck and chest and itching andburning sensations. Five days later, while still in discomfort, thepatient applied the topical preparation of the present invention andachieved prompt relief. No discomfort recurred after application of thepreparation.

CASE HISTORY NO. XII

An adult female experienced a case of shingles which exhibited symptomsof extreme pain in the upper portion of the left side of her back andextended approximately half way around to her front at the waistline.After a few days of pain, the patient broke out around the waist with apainful rash similar to chicken pox eruptions. The topical preparationof the present invention was applied, and it gave immediate greatrelief. There was no extension of the rash in contrast with an earlierexperience with shingles wherein the rash had extended to both sides ofthe patient.

CASE HISTORY NO. XIII

An adult female who was suffering from shingles was unable to lie downin bed for five days due to the pain. Application of the topicalpreparation of the present invention to the infected areas achievedprompt relief from the pain. The patient was subsequently able tonightly enjoy several hours of sleep.

CASE HISTORY NO. XIV

An adult female who was suffering severe pain from shingles achievedrelief within moments after the application of the topical preparationof the present invention. Although other preparations had previouslybeen applied, none had alleviated the unbearable pain.

CASE HISTORY NO. XV

An adult female applied the topical preparation of the present inventionto the infected regions after two weeks of suffering from shingles.Minutes after the application, the pain ceased and inflammation of thesores commenced to diminish.

While an embodiment and application of this invention has been shown anddescribed, it will be apparent to those skilled in the art that manymore modifications are possible without departing from the inventiveconcepts herein described. The invention, therefore, is not to berestricted except as is necessary by the prior art and by the spirit ofthe appended claims.

I claim:
 1. A method for the relief in humans of pain which issusceptible to topical treatment comprising the topical application tothe distressed areas of a person of an amount of an anestheticcomposition effective to relieve said pain, wherein the compositioncomprises an effective amount of at least 0.1% captan and an effectiveamount of surface active quaternary ammonium salt bactericide.
 2. Themethod of claim 1 wherein said quaternary ammonium salt is selected fromthe group consisting of, cetyl pyridinium chloride, benzalkoniumchloride, benzethonium chloride, methylbenzethonium chloride, thonzoniumbromide, triclobisonium chloride and domiphen bromide.
 3. The method ofclaim 1 wherein said composition is combined with a topical vehicle toform a topical preparation.
 4. The method of claim 3 wherein saidvehicle is selected from the group consisting of absorbent, emulsion andoleaginous ointment bases.
 5. The method of claim 3 wherein said captancomprises about 0.01 percent to about 10.0 percent by weight of saidpreparation.
 6. The method of claim 3 wherein said surface-activebactericide comprises from about 0.01 percent to about 3.0 percent byweight of said preparation.
 7. The method of claim 3 wherein saidpreparation further comprises a stabilizer.
 8. The method of claim 1wherein the anesthetic composition relieves pain which results fromminor burns, sunburn, insect bites, scratches, scrapes, minor cuts andabrasions, hives, and viral skin diseases susceptible to topicaltreatment.
 9. A method for the relief in humans of pain which issusceptible to topical treatment comprising the topical application tothe distressed areas of a person of an amount of an anestheticcomposition effective to relieve said pain wherein the compositioncomprises from about 0.01 percent to about 10.0 percent by weight ofcaptan and an effective amount of a surface-active bactericide selectedfrom the group consisting of benzalkonium chloride, benzethoniumchloride, methylbenzethonium chloride, tryclobisonium chloride, domiphenbromide.
 10. The method of claim 9 wherein said composition is combinedwith a topical vehicle to form a topical preparation.
 11. The method ofclaim 10 wherein said vehicle is selected from the group consisting ofabsorbent, emulsion and oleaginous ointment basis.
 12. The method ofclaim 10 wherein said surface active bactericide comprises from about0.01 percent to about 3.0 percent by weight of said preparation.
 13. Themethod of claim 10 wherein said preparation further comprises astabilizer.
 14. The method of claim 13 wherein said stabilizer isselected from the group consisting of butylated hydroxytoluene andtocopherol.
 15. The method of claim 13 wherein said stabilizer comprisesfrom about 0.005 percent to about 0.5 percent by weight of saidpreparation.
 16. The method of claim 9 wherein the anestheticcomposition relieves pain which results from minor burns, sunburn,insect bites, scratches, scrapes, minor cuts and abrasions, hives, andviral skin diseases susceptible to topical treatment.
 17. A method forthe relief in humans of pain which is susceptible of topical treatmentcomprising the topical application to the distressed areas of a personof an amount of an anesthetic preparation effective to relieve saidpain, said preparation comprising a topical vehicle and a chemicalcomposition including captan and benzethonium chloride, said captanbeing about 0.01 percent to about 10.0 percent by weight of saidpreparation and said benzethonium chloride being about 0.01 percent toabout 3.0 percent by weight of said preparation.
 18. A method for therelief in humans of pain which is susceptible of topical treatmentcomprising the topical application to the distressed areas of a personof an amount of an anesthetic preparation effective to relieve saidpain, said preparation comprising about 1.0 percent by weight captan,about 0.10 percent by weight benzethonium chloride, about 0.02 percentby weight butylated hydroxy toluene, and about 98.8 percent by weight ofa suitable topical vehicle.
 19. The method of claim 17 or 18 whereinsaid vehicle is selected from the group consisting of absorbent,emulsion and oleaginous ointment bases.
 20. The method of claim 17 or 18wherein the anesthetic composition relieves pain which results fromminor burns, sunburn, insect bites, scratches, scrapes, minor cuts andabrasions, hives, and viral skin diseases susceptible to topicaltreatment.